Bone Marrow Transplantation (2018) 53:1599–1602
https://doi.org/10.1038/s41409-018-0245-y
CORRESPONDENCE
Peripheral flow-MRD status at the time of autologous stem cell
collection predicts outcome in multiple myeloma
Ivana Moor
1
●
Vera U. Bacher
2
●
Barbara Jeker
1
●
Behrouz Mansouri Taleghani
2
●
Beatrice U. Mueller
3
●
Peter Keller
4
●
Daniel Betticher
5
●
Thomas Egger
6
●
Urban Novak
1
●
Thomas Pabst
1
Received: 9 February 2018 / Revised: 6 May 2018 / Accepted: 8 May 2018 / Published online: 8 June 2018
© Macmillan Publishers Limited, part of Springer Nature 2018
Flow cytometric detection of minimal residual disease (flow-
MRD) in the bone marrow is increasingly considered crucial
for monitoring myeloma (MM) patients since it can add
important information on outcome after therapy of patients
who achieve a complete remission (CR) independently of the
specific treatment compounds used [1, 2]. Advantages of such
flow-MRD assessments comprise its relative simplicity,
rapidly available results, and ubiquitous clinical applicability
[1–3]. Potential major limitations involve the lack of stan-
dardization of flow-MRD for MM patients and its decreased
sensitivity compared to PCR-based approaches [2–6]. How-
ever, the recently reported EuroFlow guidelines for next-
generation flow cytometric (NGF) MRD monitoring of MM
patients have established an increased sensitivity with a level
of detection of 10
-6
[7]. This NGF approach demonstrated a
very significant impact on PFS of MM patients, even among
those MM patients in CR or even stringent (s)CR, thereby
further improving the predictive clinical value of conventional
flow-MRD.
Although flow-MRD approaches summarized above
relied on bone marrow material, other studies investigated
the significance of the presence of clonal plasma cells in the
peripheral blood at diagnosis of MM, before or after auto-
logous stem cell transplantation (ASCT) [8, 9]. However, no
information is available so far using flow-MRD from per-
ipheral blood exactly at the day of collection of peripheral
stem cells in MM patients planned to undergo first-line
consolidation treatment with ASCT. Given the relevance of
potential malignant plasma cell contamination of the auto-
graft, we assessed the prognostic significance of circulating
aberrant plasma cells by multiparameter flow cytometry
from the peripheral blood at the day of stem cell collection.
We studied 75 consecutive MM patients in first remission
who received at least one melphalan-based high-dose che-
motherapy (HDCT) with ASCT at the University Hospital of
Bern, Switzerland, between 2010 and 2015. The majority—
80% of the patients—had received a bortezomib/dex-
amethasone based induction treatment, and the clinical char-
acteristics are summarized in Table 1. All patients have given
written informed consent, and this study was approved by the
local ethics committee of Bern, Switzerland.
Peripheral blood was analyzed by multiparameter flow
cytometry for CD34
+
cells and for clonal plasma cells at the
day of peripheral stem cell collection. Samples were investi-
gated using the BD platform (BD FACSCanto II system) and
Diva software. The following fluorochromes were used:
CD45—APC-H7; CD38—APC; CD138—PerCP; CD19—
PE-Cy7; CD56—V450; kappa—FITC; lambda—PE. Kappa
and lambda were purchased from Dako/Agilent, all other
antibodies were from BD Biosciences. The type of immu-
noglobulin and involved light chains at diagnosis were known
in all patients. The primary gating strategy included FSC,
SSC, CD45, CD38, and CD138 properties within the same
tube [9]. Aberrant phenotypic patterns were identified by
analysis of CD38, CD19, CD45, CD56 expression, and
intracytoplasmatic light chain expression [5, 10–13]. Patients
with aberrant plasma cells above 10
-5
in the peripheral blood
* Thomas Egger
thomas.pabst@insel.ch
1
Department of Medical Oncology, Inselspital, University Hospital
Bern, Bern, Switzerland
2
Department of Hematology, Inselspital, University Hospital Bern,
Bern, Switzerland
3
Department of Biomedical Research, University of Bern,
Bern, Switzerland
4
Department of Hematology, Regionalspital,
Langenthal, Switzerland
5
Department of Oncology, Kantonsspital, Fribourg, Switzerland
6
Department of Oncology, Kantonsspital, Solothurn, Switzerland
Electronic supplementary material The online version of this article
(https://doi.org/10.1038/s41409-018-0245-y) contains supplementary
material, which is available to authorized users.
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